The ability of human polymorphonuclear (PMN) leukocytes to contribute to host defense or, in other circumstances, to participate in reactions leading to tissue damage is dependent on the modulation of chemotatic migration, phagocytosis and other specialized functions including the generation of highly reactive oxygen metabolites. The molecular mechanisms of chemotaxis and chemotatic deactivation, which renders PMN leukocytes unresponsive to subsequent chemotatic stimuli, will be investigated by examining the biochemical pre-requisites of these processes, the characteristics of the membrane recognition unit for chemotactic principles and the structural and functional properties of non-chemotactic inhibitors and enhancers of leukotaxis. As diverse chemotactic and migration-enhancing factors and stimulate leukocyte oxidative metabolic pathways, the cytoregulatory and cytotoxic potentials of the highly reactive oxygen metabolites generated will studied in relation to peroxidation of membrane lipids. Disorders of leukocyte chemotaxis and oxidative metabolism will be analyzed in patients with PMN leukocyte-associated defects in host defense or leukocyte-mediated inflammatory disorders.